Damage to the integrity of a cell's DNA may occur through a variety of mechanisms. For example, DNA breakage may be caused through chemical reaction as a result of ingestion or absorption of a drug or other chemical agent that reacts with DNA (see, e.g., Exon (2007) J. Toxicol. Environ. Health B Crit. Rev. 9(5), 397-412). DNA damage may also be induced by via physical means, such as exposure to ionizing radiation (see, e.g., Brendler-Schwaab et al. (2004) Mutat. Res., 566(1): 65-91), either alone, or in combination with a chemical agent, e.g., by a photochemical mechanism.
Numerous studies suggest that certain human diseases create increase background level of oxidative DNA damage during their pathogenesis. These include, but are not limited to Alzheimer's disease (see, e.g., Mecocci et al. (1994) Ann. Neurolog. 36: 747-651; Prashad et al. (1996) Proc. Natl. Acad. Sci. USA, 93: 5146-5150), amyotrophic lateral sclerosis, Parkinson's disease, cataract formation, aging process, radiation exposure (see, e.g., Wilson et al. (1992) Cancer Res. 48: 2156-2162), ischemic damage and stroke (1996, NIH Guide 25), metal toxicity (see, e.g., Carmichael et al. (1995) Mutat. Res. 326: 235-243), breast cancer (Djuric et al. (1996) Cancer, 77: 691-696), carcinogenesis in general (see, e.g., Ames et al. (1995) Proc. Natl. Acad. Sci. USA, 92: 5258-5265). Molecular mechanisms, including the pathogenesis of oxidative DNA damage and alteration of a cell's ability to repair damaged DNA, may lead to the development of genomic instability. Genomic instability is believed to occur in an early step in the process of carcinogenesis. In addition, cells and human tissues are being screened for specific DNA damage in order to correlate the action of DNA damaging agents with human diseases and to verify the contribution of DNA damaging agents in specific genetic states to manifestation of human diseases.
Despite the utility of DNA damage analysis to determine risk for and/or prognosis of various pathologies, there are currently no systems in place for people to be able to take their blood at home and send it to a lab for DNA damage analysis. It is believed the closest to this is the RABiT (Rapid Automated Blodosimetry Tool, see, e.g., Garry et al. (2010) Health Phys. 98(2): 209-217) which is a completely automated, ultra-high throughput robotically-based biodosimetry workstation developed at Columbia University (see, e.g. cmcr.columbia.edu/rabit). RABiT uses advanced, high-speed automated image analysis and robotics to examine tissue samples (e.g., a fingerstick of blood) quickly for quantitative indicators of radiation exposure (e.g., fragments of DNA; DNA repair complexes). However, the RABiT system requires patients to be on site next to the machine and the assay is focused on radiation effects, has neglected sorting specific white cells and does not take into account the age of the person being analyzed. Knowledge and correction for these factors is in fact required for accurate interpretation of DNA damage levels. Moreover, these technologies may permit the detection of radiation hypersensitivities in humans prior to exposure to medical x-rays, such a practical capability does not currently exist.